The central nervous system (CNS) plays a key role in regulation of arterial blood pressure and an abnormality of the central neural control may result in hypertension or predispose an individual to develop hypertension in response to other factors. Studies conducted the current grant period have highlighted the role of the CNS in baroreceptor- independent long-term control of blood pressure. These studies have focused on the role of neurons in the rostral ventrolateral medulla (RVLM) in maintaining the tonic drive of sympathetic vasomotor tones are unknown. During the current grant period we have found that blockade receptors for excitatory amino acid neurotransmitters (EAA) in the RVLM will reduce blood pressure to the same extend as total autonomic blockade provide that neurons in the caudal ventrolateral medulla are inhibited. Based primarily on this observation, we have developed the hypothesis that tonically active EAA-mediated inputs to the RVLM excite RVLM-sympathoexcitatory neurons and simultaneously excite inhibitory inputs to these neurons via a circuit through the caudal ventrolateral medulla. Furthermore, we hypothesize that this balance between excitatory and inhibitory inputs to RVLM- sympathoexcitatory neurons controlled tonically by EAA-mediated inputs to the RVLM governs the long-term control of sympathetic vasomoter tone, and alteration of this balance may result in hypertension. Furthermore, based on preliminary data we proposed that the tonically- active EAA-mediated input to the RVLM comes from a specific region of the pontine reticular formation. To test these hypothesis, we propose a series of experiments to be conducted in anesthetized as well as conscious rats. Most experiments involved recording blood pressure and sympathetic nerve activity while altering the function of discrete regions of the brain stem by microinjection of neuroactive drugs. Five specific aims will be addressed: [1] to further examine the role of EAA-mediated inputs to the RVLM in the tonic regulation of sympathetic vasomotor tone; [2] to determine whether tonically-active EAA-mediated inputs to the RVLM originate from the pontine reticular formation; [3] to determine if the effects of tonically-active EAA-mediated inputs to the RVLM are altered in the chronic absence of baroreceptor feedback to the brain; [4] to determine whether the balance between excitatory and inhibitory inputs to RVLM sympathoexcitory neuron driven by tonically- active EAA-mediated inputs to the RVLM is altered in models of experimental hypertension; and [5] to begin to determine the role of the C1 population of neurons in the RVLM in mediating the responses driven by tonically-active inputs to the RVLM. These studies will contribute to our understanding of the neural control of blood pressure, and therefore may provide new insight to the pathogenesis and treatment of hypertension.